ENDOTHELIAL CELL ADHESINS OF N. MENINGITIDIS

Neisseria meningitidis is a major cause of bacterial meningitis in children
and young adults world-wide. The commercially available vaccine is not
effective against all major serogroups. In order to cause meningitis, the
bacteria must cross two host barriers. They must enter the bloodstream
from the mucosal epithelium of the nasopharynx, and from there cross the
blood/brain barrier to cause inflammation of the meninges. Meningococci
can gain access to the cerebrospinal fluid by crossing the endothelial
cells of either the meningeal capillaries or the choroid plexus. In either
case, the bacteria must interact closely with endothelial cells.
Therefore, elucidation of the molecular events that govern meningococcal
interactions with endothelial cells is crucial to our understanding of the
pathogenesis of this disease, and of the striking tropism of this bacterial
pathogen for the meninges. Identification of endothelial cell-binding
adhesins may also contribute to the development of better meningococcal
vaccines. We will study these events by identifying and characterizing bacterial
genes and gene products responsible for promoting their adherence to and
invasion of primary human endothelial cells. This will be done by standard
bacterial genetic and biochemical approaches. We will construct
meningococcal adhesion mutants, and assess their ability to invade the CSF.